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Application of Advanced Microscopic Methods to Study the Interaction of Carboxylated Fluorescent Nanodiamonds with Membrane Structures in THP-1 Cells: Activation of Inflammasome NLRP3 as the Result of Lysosome Destabilization.
- Source :
-
Molecular pharmaceutics [Mol Pharm] 2019 Aug 05; Vol. 16 (8), pp. 3441-3451. Date of Electronic Publication: 2019 Jun 24. - Publication Year :
- 2019
-
Abstract
- Nanodiamonds (ND), especially fluorescent NDs, represent potentially applicable drug and probe carriers for in vitro/in vivo applications. The main purpose of this study was to relate physical-chemical properties of carboxylated NDs to their intracellular distribution and impact on membranes and cell immunity-activation of inflammasome in the in vitro THP-1 cell line model. Dynamic light scattering, nanoparticle tracking analysis, and microscopic methods were used to characterize ND particles and their intracellular distribution. Fluorescent NDs penetrated the cell membranes by both macropinocytosis and mechanical cutting through cell membranes. We proved accumulation of fluorescent NDs in lysosomes. In this case, lysosomes were destabilized and cathepsin B was released into the cytoplasm and triggered pathways leading to activation of inflammasome NLRP3, as detected in THP-1 cells. Activation of inflammasome by NDs represents an important event that could underlie the described toxicological effects in vivo induced by NDs. According to our knowledge, this is the first in vitro study demonstrating direct activation of inflammasome by NDs. These findings are important for understanding the mechanism(s) of action of ND complexes and explain the ambiguity of the existing toxicological data.
- Subjects :
- Cathepsin B immunology
Cathepsin B metabolism
Cell Membrane drug effects
Cell Membrane metabolism
Cell Membrane ultrastructure
Dynamic Light Scattering
Fluorescence
Humans
Inflammasomes immunology
Inflammasomes metabolism
Lysosomes immunology
Lysosomes metabolism
Lysosomes ultrastructure
Microscopy, Atomic Force
Microscopy, Confocal
Microscopy, Electron
NLR Family, Pyrin Domain-Containing 3 Protein immunology
Nanodiamonds chemistry
Pinocytosis
THP-1 Cells
Inflammasomes drug effects
Intravital Microscopy methods
Lysosomes drug effects
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Nanodiamonds administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1543-8392
- Volume :
- 16
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Molecular pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 31184896
- Full Text :
- https://doi.org/10.1021/acs.molpharmaceut.9b00225